Aging, Lifespan & Longevity

Biomarkers of ageing and frailty may predict COVID-19 severity

21 hours 39 minutes ago
Coronavirus Disease 2019 (COVID-19) is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) - the culprit of an ongoing pandemic responsible for the loss of over 3 million lives worldwide within a year and a half. While the majority of SARS-CoV-2 infected people develop no or mild symptoms, some become severely ill and may die from COVID-19-related complications. In this review, we compile and comment on a number of biomarkers that have been identified...
Kailyn J Wanhella

Transcranial Magnetic Stimulation (TMS) for Geriatric Depression

21 hours 39 minutes ago
CONCLUSIONS: The reviewed literature highlights large heterogeneity among studies both in terms of the employed TMS dosage and the observed clinical efficacy. This highlights the need for optimizing TMS dosage by recognizing the unique clinical features of GD. We showcase a set of novel approaches for the optimization of the TMS protocol for depression and discuss the possibility for a standardized TMS protocol tailored for the treatment of GD.
Davide Cappon

Metformin treatment of diverse Caenorhabditis species reveals the importance of genetic background in longevity and healthspan extension outcomes

1 day 21 hours ago
Metformin, the most commonly prescribed anti-diabetes medication, has multiple reported health benefits, including lowering the risks of cardiovascular disease and cancer, improving cognitive function with age, extending survival in diabetic patients, and, in several animal models, promoting youthful physiology and lifespan. Due to its longevity and health effects, metformin is now the focus of the first proposed clinical trial of an anti-aging drug-the Targeting Aging with Metformin (TAME)...
Brian Onken

Microglial PD-1 stimulation by astrocytic PD-L1 suppresses neuroinflammation and Alzheimer's disease pathology

2 days 21 hours ago
Chronic neuroinflammation is a pathogenic component of Alzheimer's disease (AD) that may limit the ability of the brain to clear amyloid deposits and cellular debris. Tight control of the immune system is therefore key to sustain the ability of the brain to repair itself during homeostasis and disease. The immune-cell checkpoint receptor/ligand pair PD-1/PD-L1, known for their inhibitory immune function, is expressed also in the brain. Here, we report upregulated expression of PD-L1 and PD-1 in...
Markus P Kummer

Phenotype correlations reveal the relationships of physiological systems underlying human ageing

2 days 21 hours ago
Ageing is characterized by degeneration and loss of function across multiple physiological systems. To study the mechanisms and consequences of ageing, several metrics have been proposed in a hierarchical model, including biological, phenotypic and functional ageing. In particular, phenotypic ageing and interconnected changes in multiple physiological systems occur in all ageing individuals over time. Recently, phenotypic age, a new ageing measure, was proposed to capture morbidity and mortality...
Meng Hao

Hematopoiesis under telomere attrition at the single-cell resolution

2 days 21 hours ago
The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under...
Natthakan Thongon

Dietary essential amino acids restore liver metabolism in ovariectomized mice via hepatic estrogen receptor α

2 days 21 hours ago
In female mammals, the cessation of ovarian functions is associated with significant metabolic alterations, weight gain, and increased susceptibility to a number of pathologies associated with ageing. The molecular mechanisms triggering these systemic events are unknown because most tissues are responsive to lowered circulating sex steroids. As it has been demonstrated that isoform alpha of the estrogen receptor (ERα) may be activated by both estrogens and amino acids, we test the metabolic...
Sara Della Torre

From structure to clinic: Design of a muscarinic M1 receptor agonist with potential to treatment of Alzheimer's disease

3 days 21 hours ago
Current therapies for Alzheimer's disease seek to correct for defective cholinergic transmission by preventing the breakdown of acetylcholine through inhibition of acetylcholinesterase, these however have limited clinical efficacy. An alternative approach is to directly activate cholinergic receptors responsible for learning and memory. The M1-muscarinic acetylcholine (M1) receptor is the target of choice but has been hampered by adverse effects. Here we aimed to design the drug properties...
Alastair J H Brown

TBX2 controls a proproliferative gene expression program in melanoma

3 days 21 hours ago
Senescence shapes embryonic development, plays a key role in aging, and is a critical barrier to cancer initiation, yet how senescence is regulated remains incompletely understood. TBX2 is an antisenescence T-box family transcription repressor implicated in embryonic development and cancer. However, the repertoire of TBX2 target genes, its cooperating partners, and how TBX2 promotes proliferation and senescence bypass are poorly understood. Here, using melanoma as a model, we show that TBX2 lies...
Sizhu Lu

Three-dimensional virtual histology of the human hippocampus based on phase-contrast computed tomography

3 days 21 hours ago
We have studied the three-dimensional (3D) cytoarchitecture of the human hippocampus in neuropathologically healthy and Alzheimer's disease (AD) individuals, based on phase-contrast X-ray computed tomography of postmortem human tissue punch biopsies. In view of recent findings suggesting a nuclear origin of AD, we target in particular the nuclear structure of the dentate gyrus (DG) granule cells. Tissue samples of 20 individuals were scanned and evaluated using a highly automated approach of...
Marina Eckermann

Synergistic insights into human health from aptamer- and antibody-based proteomic profiling

3 days 21 hours ago
Affinity-based proteomics has enabled scalable quantification of thousands of protein targets in blood enhancing biomarker discovery, understanding of disease mechanisms, and genetic evaluation of drug targets in humans through protein quantitative trait loci (pQTLs). Here, we integrate two partly complementary techniques-the aptamer-based SomaScan^(®) v4 assay and the antibody-based Olink assays-to systematically assess phenotypic consequences of hundreds of pQTLs discovered for 871 protein...
Maik Pietzner

Nogo receptor impairs the clearance of fibril amyloid-beta by microglia and accelerates Alzheimer's-like disease progression

3 days 21 hours ago
Alzheimer's disease (AD) is characterized by the progressive accumulation of β-amyloid (Aβ)-containing amyloid plaques, and microglia play a critical role in mediating Aβ clearance. Mounting evidence has confirmed that the ability of microglia in clearing Aβ decreased with aging and AD progress, but the underlying mechanisms are unclear. Previously, we have demonstrated that Nogo receptor (NgR), a receptor for three axon growth inhibitors associated with myelin, can decrease adhesion and...
Jianing Wang

Stem cell aging in the skeletal muscle: the importance of communication

4 days 21 hours ago
Adult stem cells sustain tissue homeostasis and regeneration; their functional decline is often linked to aging, which is characterized by the progressive loss of physiological functions across multiple tissues and organs. The resident stem cells in skeletal muscle, termed satellite cells, are normally quiescent but activate upon injury to reconstitute the damaged tissue. In this review, we discuss the current understanding of the molecular processes that contribute to the functional failure of...
Xiaotong Hong

Amyloid β 42 fibril structure based on small-angle scattering

4 days 21 hours ago
Amyloid fibrils are associated with a number of neurodegenerative diseases, including fibrils of amyloid β42 peptide (Aβ42) in Alzheimer's disease. These fibrils are a source of toxicity to neuronal cells through surface-catalyzed generation of toxic oligomers. Detailed knowledge of the fibril structure may thus facilitate therapeutic development. We use small-angle scattering to provide information on the fibril cross-section dimension and shape for Aβ42 fibrils prepared in aqueous phosphate...
Veronica Lattanzi

Targeting p21<sup>Cip1</sup> highly expressing cells in adipose tissue alleviates insulin resistance in obesity

5 days 21 hours ago
Insulin resistance is a pathological state often associated with obesity, representing a major risk factor for type 2 diabetes. Limited mechanism-based strategies exist to alleviate insulin resistance. Here, using single-cell transcriptomics, we identify a small, critically important, but previously unexamined cell population, p21^(Cip1) highly expressing (p21^(high)) cells, which accumulate in adipose tissue with obesity. By leveraging a p21-Cre mouse model, we demonstrate that intermittent...
Lichao Wang

Deregulated mitochondrial microRNAs in Alzheimer's disease: Focus on synapse and mitochondria

5 days 21 hours ago
Alzheimer's disease (AD) is the most common cause of dementia and is currently one of the biggest public health concerns in the world. Mitochondrial dysfunction in neurons is one of the major hallmarks of AD. Emerging evidence suggests that mitochondrial miRNAs potentially play important roles in the mitochondrial dysfunctions, focusing on synapse in AD progression. In this meta-analysis paper, a comprehensive literature review was conducted to identify and discuss the (1) role of mitochondrial...
Prashanth Gowda

Frailty and pain, human studies and animal models

5 days 21 hours ago
The hypothesis that pain can predispose to frailty development has been recently investigated in several clinical studies suggesting that frailty and pain may share some mechanisms. Both pain and frailty represent important clinical and social problems and both lack a successful treatment. This circumstance is mainly due to the absence of in-depth knowledge of their pathological mechanisms. Evidence of shared pathways between frailty and pain are preliminary. Indeed, many clinical studies are...
Simona D'Agnelli

Cisd2 slows down liver aging and attenuates age-related metabolic dysfunction in male mice

5 days 21 hours ago
The liver plays a pivotal role in mammalian aging. However, the mechanisms underlying liver aging remain unclear. Cisd2 is a pro-longevity gene in mice. Cisd2 mediates lifespan and healthspan via regulation of calcium homeostasis and mitochondrial functioning. Intriguingly, the protein level of Cisd2 is significantly decreased by about 50% in the livers of old male mice. This down-regulation of Cisd2 may result in the aging liver exhibiting non-alcoholic fatty liver disease (NAFLD) phenotype....
Yi-Long Huang

Growth hormone receptor gene disruption in mature-adult mice improves male insulin sensitivity and extends female lifespan

5 days 21 hours ago
Studies in multiple species indicate that reducing growth hormone (GH) action enhances healthy lifespan. In fact, GH receptor knockout (GHRKO) mice hold the Methuselah prize for the world's longest-lived laboratory mouse. We previously demonstrated that GHR ablation starting at puberty (1.5 months), improved insulin sensitivity and female lifespan but results in markedly reduced body size. In this study, we investigated the effects of GHR disruption in mature-adult mice at 6 months old...
Silvana Duran-Ortiz
1 hour 29 minutes ago
Aging, Lifespan & Longevity
Aging: Latest results from PubMed
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